Methods, compositions, and uses of novel Fyn kinase inhibitors

Abstract

The present invention provides methods for inhibiting Fyn kinase, using 5-3-pyridin-2-amine, 6-3-imidazo[1,2-a] pyrazine, 6-3-imidazo[1,2-b] pyridazine, N-(5-imidazo [2,1-b][1,3,4] thiadiazol-2-yl)-amine, 4-3-1H-pyrazolo[3,4-b] pyridine, and N-(3-imidazo [1,2-b] pyridazin-6-yl) amine compounds and methods of treatment, prevention, inhibition or amelioration of diseases and conditions associated with Fyn kinase using such compounds.

I claim: 
     
       1. A method of treating a condition associated with Fyn kinase activity, said method comprising administering a therapeutically effective amount of at least one compound, or pharmaceutically acceptable salt or solvate of the compound to a patient in need thereof, wherein the compound is selected from N-[3-(dimethyl-amino)-propyl]-4-[3-(4-hydroxy-phenyl)-imidazo[1,2-a]pyrazin-6-yl]-benzamide, N-[2-(dimethyl-amino)-ethyl]-4-[3-(4-hydroxy-phenyl)-imidazo[1,2-a]pyrazin-6-yl]-benzamide, N-(2-hydroxy-ethyl)-4-[3-(4-hydroxy-phenyl)-imidazo[1,2-a]pyrazin-6-yl]benzamide, N-[3-(dimethyl-amino)-propyl]-4-[3-(4-hydroxy-3-methoxy-phenyl)-imidazo[1,2-a]pyrazin-6-yl]benzamide, N-(2-hydroxy-ethyl)-3-[3-(4-hydroxy-3-methoxy-phenyl)-imidazo[1,2-a]pyrazin-6-yl]benzamide, N-[2-(dimethyl-amino)ethyl]-4-[3-(4-phenoxy-phenyl)-imidazo[1,2-a]pyrazin-6-yl]-benzamide, N-[3-(dimethyl-amino)-propyl]-4-[3-(4-phenoxy-phenyl) imidazo[1,2-a]pyrazin-6-yl]benzamide, N-[2-(dimethyl-amino)ethyl]-4-[3-(4-hydroxy-3-methoxy-phenyl)-imidazo[1,2-a]pyrazin-6-yl]benzamide, N-(2-hydroxy-ethyl)-4-[3-(4-phenoxy-phenyl)-imidazo-[1,2-a]-pyrazin-6-yl]benzamide, and 3-[3-(4-hydroxy-phenyl)-imidazo[1,2-a]pyrazin-6-yl]-N,N-dimethyl-benzamide, wherein the condition associated with Fyn kinase activity is selected from Type 1 diabetes, Type II diabetes, pre-diabetes, and obesity. 
     
     
       2. The method of  claim 1  wherein the compound described in Table 4 of the description is N-[3-(dimethylamino)propyl]-4-[3-(4-phenoxyphenyl)imidazo[1,2-a]pyrazin-6-yl]benzamide. 
     
     
       3. The method of  claim 1  wherein the compound described in Table 4 of the description is N-[2-(dimethylamino)ethyl]-4-[3-(4-phenoxyphenyl)imidazo [1,2-a]pyrazin-6-yl]benzamide. 
     
     
       4. A method of inhibiting the activity of Fyn kinase in a cell or a subject, comprising administering to the cell or subject an effective amount of a compound selected from N-[3-(dimethyl-amino)-propyl]-4-[3-(4-hydroxy-phenyl)-imidazo[1,2-a]pyrazin-6-yl]-benzamide, N-[2-(dimethyl-amino)-ethyl]-4-[3-(4-hydroxy-phenyl)-imidazo[1,2-a]pyrazin-6-yl]-benzamide, N-(2-hydroxy-ethyl)-4-[3-(4-hydroxy-phenyl)-imidazo[1,2-a]pyrazin-6-yl]benzamide, N-[3-(dimethyl-amino)-propyl]-4-[3-(4-hydroxy-3-methoxy-phenyl)-imidazo[1,2-a]pyrazin-6-yl]benzamide, N-(2-hydroxy-ethyl)-3-[3-(4-hydroxy-3-methoxy-phenyl)-imidazo[1,2-a]pyrazin-6-yl]benzamide, N-[2-(dimethyl-amino)ethyl]-4-[3-(4-phenoxy-phenyl)-imidazo[1,2-a]pyrazin-6-yl]-benzamide, N-[3-(dimethyl-amino)-propyl]-4-[3-(4-phenoxy-phenyl) imidazo[1,2-a]pyrazin-6-yl]benzamide, N-[2-(dimethyl-amino)ethyl]-4-[3-(4-hydroxy-3-methoxy-phenyl)-imidazo[1,2-a]pyrazin-6-yl]benzamide, N-(2-hydroxy-ethyl)-4-[3-(4-phenoxy-phenyl)-imidazo-[1,2-a]-pyrazin-6-yl]benzamide, and 3-[3-(4-hydroxy-phenyl)-imidazo[1,2-a]pyrazin-6-yl]-N,N-dimethyl-benzamide, or a pharmaceutically acceptable salt or solvate thereof. 
     
     
       5. The method of  claim 4 , wherein the subject has a disease selected from Type I diabetes, Type II diabetes, and obesity.